title: PPAR activation as a regulator of lipid metabolism, nitric oxide production and lipid peroxidation in the placenta from type 2 diabetic patients.
abstract: Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, anti-inflammatory processes and placental development. Maternal diabetes induces a pro-inflammatory environment and alters placental development. We investigated whether PPARs regulate lipid metabolism and nitric oxide (NO) production in placental explants from healthy and type 2 diabetic (DM2) patients. We found decreased PPARα and PPARγ concentrations, no changes in PPARδ concentrations, and increased lipids, lipoperoxides and NO production in placentas from DM2 patients. PPARα agonists reduced placental concentrations of triglycerides and both PPARα and PPARδ agonists reduced concentrations of phospholipids, cholesteryl esters and cholesterol. PPARγ agonists increased lipid concentrations in placentas from DM2 patients and more markedly in placentas from healthy patients. Endogenous ligands for the three PPAR isotypes reduced NO production and lipoperoxidation in placentas from DM2 patients. We conclude that PPARs play a role in placental NO and lipid homeostasis and can regulate NO production, lipid concentrations and lipoperoxidation in placentas from DM2 patients.
authors.affiliation: Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.forename: Nora
authors.initials: N
authors.lastname: Martínez
authors.forename: Daiana
authors.initials: D
authors.lastname: Fornes
authors.forename: Romina
authors.initials: R
authors.lastname: Higa
authors.forename: Ingrid
authors.initials: I
authors.lastname: Di Marco
authors.forename: María Natalia
authors.initials: MN
authors.lastname: Basualdo
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Faingold
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
mesh_terms: D000328:Adult; D015153:Blotting, Western; D003720:Densitometry; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D009569:Nitric Oxide / Q000096:biosynthesis*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide
keywords: 15dPGJ(2); 15deoxyΔ(12,14)PGJ(2); Clof; Diabetes in pregnancy; GDM; GW; GW501516; LTB(4); Lipid metabolism; NO; Nitric oxide; PG; PGI(2); PPAR; PPARs; Placenta; Rosi; TBARS; cPGI(2); carbaprostacyclin; clofibrate; gestational diabetes mellitus; leukotriene B(4); nitric oxide; peroxisome proliferator activated receptor; prostacyclin or prostaglandin I(2); prostaglandin; rosiglitazone; thiobarbituric acid reactive substances